Publications by authors named "Ainsley Mike Antao"

5 Publications

  • Page 1 of 1

The Role of Nkx3.1 in Cancers and Stemness.

Int J Stem Cells 2021 Feb 28. Epub 2021 Feb 28.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Korea.

The well-known androgen-regulated homeobox gene, , is located on the short arm of chromosome 8. It is the first known prostate epithelium-specific marker, and is a transcription factor involved in development of the testes and prostate. In addition to specifying the prostate epithelium and maintaining normal prostate secretory function, Nkx3.1 is an established marker for prostate cancer. Over the years, however, this gene has been implicated in various other cancers, and technological advances have allowed determination of its role in other cellular functions. Nkx3.1 has also been recently identified as a factor capable of replacing Oct4 in cellular reprogramming. This review highlights the role of this tumor suppressor and briefly describes its functions, ranging from prostate development to maintenance of stemness and cellular reprogramming.
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http://dx.doi.org/10.15283/ijsc20121DOI Listing
February 2021

Disease modeling and stem cell immunoengineering in regenerative medicine using CRISPR/Cas9 systems.

Comput Struct Biotechnol J 2020 19;18:3649-3665. Epub 2020 Nov 19.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.

CRISPR/Cas systems are popular genome editing tools that belong to a class of programmable nucleases and have enabled tremendous progress in the field of regenerative medicine. We here outline the structural and molecular frameworks of the well-characterized type II CRISPR system and several computational tools intended to facilitate experimental designs. The use of CRISPR tools to generate disease models has advanced research into the molecular aspects of disease conditions, including unraveling the molecular basis of immune rejection. Advances in regenerative medicine have been hindered by major histocompatibility complex-human leukocyte antigen (HLA) genes, which pose a major barrier to cell- or tissue-based transplantation. Based on progress in CRISPR, including in recent clinical trials, we hypothesize that the generation of universal donor immune-engineered stem cells is now a realistic approach to tackling a multitude of disease conditions.
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http://dx.doi.org/10.1016/j.csbj.2020.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710510PMC
November 2020

E3 Ubiquitin Ligase APC/C Regulation of Phenylalanine Hydroxylase Stability and Function.

Int J Mol Sci 2020 Nov 28;21(23). Epub 2020 Nov 28.

Department of Biomedical Science, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by the dysfunction of the enzyme phenylalanine hydroxylase (PAH). Alterations in the level of PAH leads to the toxic accumulation of phenylalanine in the blood and brain. Protein degradation mediated by ubiquitination is a principal cellular process for maintaining protein homeostasis. Therefore, it is important to identify the E3 ligases responsible for PAH turnover and proteostasis. Here, we report that anaphase-promoting complex/cyclosome-Cdh1 (APC/C) is an E3 ubiquitin ligase complex that interacts and promotes the polyubiquitination of PAH through the 26S proteasomal pathway. Cdh1 destabilizes and declines the half-life of PAH. In contrast, the CRISPR/Cas9-mediated knockout of stabilizes PAH expression and enhances phenylalanine metabolism. Additionally, our current study demonstrates the clinical relevance of PAH and Cdh1 correlation in hepatocellular carcinoma (HCC). Overall, we show that PAH is a prognostic marker for HCC and Cdh1 could be a potential therapeutic target to regulate PAH-mediated physiological and metabolic disorders.
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http://dx.doi.org/10.3390/ijms21239076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729981PMC
November 2020

Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.

Cancers (Basel) 2020 Jun 15;12(6). Epub 2020 Jun 15.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul 04763, Korea.

Since the discovery of the ubiquitin proteasome system (UPS), the roles of ubiquitinating and deubiquitinating enzymes (DUBs) have been widely elucidated. The ubiquitination of proteins regulates many aspects of cellular functions such as protein degradation and localization, and also modifies protein-protein interactions. DUBs cleave the attached ubiquitin moieties from substrates and thereby reverse the process of ubiquitination. The dysregulation of these two paramount pathways has been implicated in numerous diseases, including cancer. Attempts are being made to identify inhibitors of ubiquitin E3 ligases and DUBs that potentially have clinical implications in cancer, making them an important target in the pharmaceutical industry. Therefore, studies in medicine are currently focused on the pharmacological disruption of DUB activity as a rationale to specifically target cancer-causing protein aberrations. Here, we briefly discuss the pathophysiological and physiological roles of DUBs in key cancer-related pathways. We also discuss the clinical applications of promising DUB inhibitors that may contribute to the development of DUBs as key therapeutic targets in the future.
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http://dx.doi.org/10.3390/cancers12061579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352412PMC
June 2020

Deubiquitinating enzymes in cancer stem cells: functions and targeted inhibition for cancer therapy.

Drug Discov Today 2018 12 1;23(12):1974-1982. Epub 2018 Jun 1.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; College of Medicine, Hanyang University, Seoul, South Korea. Electronic address:

The ability of cancers to evade conventional treatments, such as chemotherapy and radiation therapy, has been attributed to a subpopulation of cancer stem cells (CSCs). CSCs are regulated by mechanisms similar to those that regulate normal stem cells (NSCs), including processes involving ubiquitination and deubiquitination enzymes (DUBs) that regulate the expression of various factors, such as Notch, Wnt, Sonic Hedgehog (Shh), and Hippo. In this review, we discuss the roles of various DUBs involved in the regulation of core stem cell transcription factors and CSC-related proteins that are implicated in the modulation of cellular processes and carcinogenesis. In addition, we discuss the various DUB inhibitors that have been designed to target processes relevant to cancer and CSC maintenance.
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http://dx.doi.org/10.1016/j.drudis.2018.05.035DOI Listing
December 2018